Study of A Combination Pill With GS-7977 and GS-5885 for Hepatitis C in People With HIV

This study has been completed.

Sponsor:

National Institute of Allergy and Infectious Diseases (NIAID)

ClinicalTrials.gov Identifier:

NCT01878799

First Posted: June 17, 2013

Last Update Posted: September 15, 2016

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government.
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- Present treatment for hepatitis C includes the use of a weekly injection and two different pills. This treatment is associated with serious side effects. Drugs that can be taken by mouth and cure HCV infection without serious side effects would be a great help to the large number of people infected with HCV. GS-7977 and GS-5885 are new medications being developed to treat the hepatitis C virus (HCV) infection. They are still being researched and are not approved by the Food and Drug Administration. They are being developed as treatment for hepatitis C as a single pill taken once a day.

Objectives:

- To determine whether a combination of the two study drugs can safely and effectively treat HCV infection in people with HIV infection and who do not have cirrhosis of the liver.

Eligibility:

- Individuals who have HIV infection and have liver disease caused by infection with HCV.

Design:

Participants will be screened with a physical exam and medical history. Blood samples will be collected. Urine samples will be collected from participants who might become pregnant. If a participant has not had a liver biopsy in the past 3 years, one will be required.

Participants will take one pill daily for 12 weeks. This pill will be a combination of the two study drugs.

Treatment will be monitored with frequent clinic visits and blood tests over a total of 60 weeks.

The primary end point was sustained virologic response [plasma HCV RNA level <12 IU/mL by real-time HCV assay (Abbott)] at 12 weeks after treatment completion (SVR12) among all patients enrolled in the study.

The GS-7977/GS-5885 FDC product combines a potent HCV nucleotide inhibitor and a potent HCV NS5A inhibitor and will be given for 12 weeks.

Detailed Description:

Chronic hepatitis C virus (HCV) infection is a major public health problem with an estimated 180 million people infected worldwide. In the US an estimated 4.1 million people are infected with HCV which is the principal cause of death from liver disease and leading indication for liver transplantation. Significant advances have been made with the approval of directly acting antivirals (DAA) namely the protease inhibitors, telaprevir (TVR) and boceprevir (BOC) which have been shown to significantly improve rates of sustained virologic response (SVR). Response rates to these new combinations in HIV/HCV are also very promising, however treatment has been characterized with high rates of toxicities.

Recently several trials have confirmed the efficacy of potent DAA therapy without concomitant IFN in the treatment of HCV monoinfected individuals. Given the improved response rates achieved with a combination of DAAs with fast HCV suppression and improved side-effect profiles; and the need for better therapy for HIV/HCV co-infected subjects, we propose a study to determine the safety, tolerability and efficacy of 12 weeks of treatment with a fixed dose combination of GS-7977 and GS-5885 in HIV/HCV Genotype 1 (GT-1) subjects. We hypothesize that anti-HCV therapy that does not rely on the host immune system will provide an enhanced rate of SVR among HIV/HCV GT-1 coinfected subjects. The findings from this study will aid in our understanding of determinants of response to an IFN-free regimen in HIV/HCV coinfected individuals.

Eligibility

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Ages Eligible for Study:

18 Years and older (Adult, Senior)

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

No

Criteria

INCLUSION CRITERIA:

Eighteen years of age or older at screening.

HCV treatment-naive, as defined as no prior exposure to any IFN, RBV, or other approved or experimental HCV-specific direct-acting antiviral agent.

Participants must be willing to practice either:

Abstinence from sexual intercourse or

At least 2 forms of contraception including one barrier method from 2 weeks prior to Day 0 through 30 days after the last dose is received.

i. Female partners of male study subjects may rely upon hormonal contraception as one of the 2 methods; however female study subjects may not.

Chronic hepatitis C infection defined as one of the following:

Positive for anti-HCV antibody, HCV RNA, or an HCV genotype at least 6 months before screening, and positive for HCV RNA and anti-HCV antibody at the time of screening or

Positive for anti-HCV antibody and HCV RNA at the time of screening with a liver biopsy consistent with chronic HCV infection (or a liver biopsy performed before enrollment with evidence of chronic hepatitis C disease, such as the presence of fibrosis).

a CD4 T-cell count greater than or equal to 500 cells/mm3 within 8 weeks of Day 0 or

an HIV viral load less than 500 copies/mL with a stable CD4 count for at least 3 months.

Documented HIV infection on a stable, protocol-approved, ARV regimen for greater than or equal to 8 weeks prior to dosing and is expected to continue the current ARV regimen through the end of study with all of the following:

a CD4 T-cell count > 100 cells/mm3

a documented plasma HIV-1 RNA level less than the level of detection for at least 8 weeks preceding dosing.

HIV ARV agents including only combination regimens consisting of medications from the following list: tenofovir (TDF), emtricitabine (FTC), efavirenz, raltegravir, and rilpivirine administered according to their manufacturer s prescribing information. (reference Section 10.3 for additional information)

Documentation of hepatitis C genotype 1a, 1b or mixed 1a/1b

Absence of cirrhosis, defined as one of the following:

A liver biopsy performed within 36 calendar months of screening showing absence of cirrhosis.

FibroTest score of < 0.48 AND APRI of < 1 performed during the 8 weeks preceding dosing (In the absence of a definitive diagnosis of presence or absence of cirrhosis by the above criteria, a liver biopsy is required).

Able to effectively communicate with the Investigator and other center personnel.

Willing to give written informed consent and comply with the study restrictions and requirements.

If opioid-dependent, subjects must be participating in a supervised treatment.

Participants must have a primary medical provider outside of OP8 and the NIH for medical management.

EXCLUSION CRITERIA:

Subjects who meet any of the following exclusion criteria are not to be enrolled in this study:

Current or prior history of any of the following:

Clinically significant illness (other than HCV) or any other major medical disorder that may interfere with subject treatment, assessment or compliance with the protocol; subjects currently under evaluation for a potentially clinically-significant illness (other than HCV) are also excluded.

Gastrointestinal disorder or post-operative condition that could interfere with the absorption of the study drug.

Patients with renal impairment or uncontrolled medical problems that could place them at high risk for developing renal impairment.

Positive test at screening for either HBsAg or quantifiable HBV DNA (completed only if necessary to rule out chronic HBV)

Current use of non-protocol approved ARVs.

A new AIDS-defining condition diagnosed within 30 days prior to screening or active, serious infection (other than HIV or HCV) requiring parenteral antibiotics, antivirals or antifungals within 30 days prior to Day 0.

Cirrhosis of the liver

Screening or baseline ECG with clinically significant ECG findings.

Abnormal hematological and biochemical parameters, including:

Neutrophil count < 750 cells/mm(3)

Hemoglobin < 9 g/dL. If Hgb is < 11g/dL in women or < 12 g/dL in men. Other causes of anemia should be excluded as medically indicated.

Platelet count less than or equal to 50,000 cells/mm(3)

Estimated GFR (calculated by the CKD-EP(I) equation) < 50 mL/min/per 1.73 m(2) if not on ARV or < 60 mL/min if on ARVs

ALT or AST greater than or equal to 10 times ULN

Serum lipase greater than or equal to 1.5 times ULN (at screening or during the screening period)

Direct bilirubin greater than or equal to 1.50 times ULN

Albumin less than or equal to 3.0 g/dL

INR greater than or equal to 1.5 times ULN unless subject has known hemophilia or is stable on an anticoagulant regimen affecting INR.

Donation or loss of more than 400 mL blood within 8 weeks prior to first dose administration.

Medications for disease conditions excluded from the protocol (e.g., active cancer, transplantation) are not listed under this Concomitant Medication section and are disallowed in the study.

Concomitant use of certain medications or herbal/natural supplements per PI discretion expected to result in pharmacokinetic interactions resulting in increases or decreases in exposure of study drug(s) as listed in Table of this protocol.

Contacts and Locations

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01878799